Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7327
pubmed:dateCreated
2010-12-23
pubmed:abstractText
Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency >?1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
468
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1061-6
pubmed:dateRevised
2011-10-21
pubmed:meshHeading
pubmed-meshheading:21179162-Animals, pubmed-meshheading:21179162-Brain, pubmed-meshheading:21179162-Case-Control Studies, pubmed-meshheading:21179162-Cell Line, pubmed-meshheading:21179162-Female, pubmed-meshheading:21179162-Finland, pubmed-meshheading:21179162-Founder Effect, pubmed-meshheading:21179162-Gene Expression Regulation, pubmed-meshheading:21179162-Gene Knockout Techniques, pubmed-meshheading:21179162-Genotype, pubmed-meshheading:21179162-Humans, pubmed-meshheading:21179162-Impulsive Behavior, pubmed-meshheading:21179162-Male, pubmed-meshheading:21179162-Mental Disorders, pubmed-meshheading:21179162-Mice, pubmed-meshheading:21179162-Mice, 129 Strain, pubmed-meshheading:21179162-Mice, Knockout, pubmed-meshheading:21179162-Pedigree, pubmed-meshheading:21179162-Polymorphism, Single Nucleotide, pubmed-meshheading:21179162-Receptor, Serotonin, 5-HT2B, pubmed-meshheading:21179162-Testosterone
pubmed:year
2010
pubmed:articleTitle
A population-specific HTR2B stop codon predisposes to severe impulsivity.
pubmed:affiliation
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland 20852, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural